复幼颗粒剂对大鼠的单次给药毒性及幼龄动物重复给药毒性试验研究

Study on the Single Dose Toxicity on Rats and Repeated Dose Toxicity on Juvenile Animals of Fuyou Granules on Rats

关键词:  复幼颗粒  医院制剂  单次给药毒性  重复给药毒性  幼龄动物

Key words:  Fuyou granules  hospital preparation  single toxicity  repeated dose toxicity  juvenile animals

摘要:

目的 评价复幼颗粒对SD大鼠的非临床安全性。方法 单次给药毒性试验：20只SD大鼠(6~7周龄)，随机分为溶媒对照组(去离子水)和复幼颗粒组(18 g·kg^-1)，按每次30 mL·kg^-1灌胃给药，24 h给药2次(上、下午)，给药后观察14 d；检查项目包括临床观察、体质量、大体解剖等。重复给药毒性试验：将192只幼龄SD大鼠(出生后4 d)按体质量随机分为溶媒对照组(去离子水)，低、中、高剂量复幼颗粒组(1.2，2.5，5 g·kg^-1)，按每次10 mL·kg^-1灌胃给药，每天2次，连续给药13周，恢复期4周；检查项目包括一般生理指标、眼科检查、发育指标、血液生化指标、免疫学指标、激素指标、生殖功能指标、组织病理学观察等。结果 单次给药毒性试验：SD大鼠灌胃给予复幼颗粒按18 g·kg^-1(生药：82 g·kg^-1)，无明显急性毒性。重复给药毒性试验：幼龄SD大鼠灌胃给予2.5 g·kg^-1(生药：11.33 g·kg^-1)复幼颗粒连续给药13周，未见明显毒性反应。恢复期高剂量组雌鼠孕酮水平显著降低。结论 复幼颗粒对受试动物在临床拟用剂量范围内未见明显的单次给药毒性和重复给药毒性反应。

Abstract:

OBJECTIVE To evaluate the non-clinical safety of Fuyou granules on SD rats. METHODS For single toxicity experiment, 20 SD rats(6-7 weeks old) were randomly divided into two groups. The rats in the vehicle control group were given deionized water by gavage, and those in the Fuyou group were given Fuyou granules at the dose of 18 g·kg^-1 in a volume of 30 mL·kg^-1 per time, twice in 24 h(in the morning and afternoon), and observation was performed for 14 d after administration. Test items included clinical observation, body mass, gross anatomy, etc. For repeated dose toxicity test, 192 juvenile SD rats(postnatal day 4) were randomly divided into vehicle control group(deionized water) and low, medium and high dose of Fuyou granules groups (1.2, 2.5, 5 g·kg^-1) according to body mass. The rats were orally administered twice daily with vehicle or Fuyou granules for 13 weeks in volume of 10 mL·kg^-1 per time. A recovery period of 4 weeks was followed. Test items included general physiological indexes, ophthalmic examination, development indicators, hematology and biochemical indicators, immunological indicators, hormone indicators, reproductive function and histopathological examinations. RESULTS In the single toxicity experiment, at the dose of 18 g·kg^-1(raw drug: 82 g·kg^-1), Fuyou granules did not show significant acute toxicity in rats. In the repeated dose toxicity test, juvenile SD rats were given Fuyou granules by gavage for 13 weeks, and no significant toxic reaction was observed at the dose level of 2.5 g·kg^-1(raw drug: 11.33 g·kg^-1). The progesterone level of female rats in the high-dose group decreased significantly after recovery period. CONCLUSION Fuyou granules have no obvious single and repeated dose toxicity effects on rats in the clinical dose range．